Réaction #653183

Équation de réaction

sulfuric acid

4-ethylbromobenzene

n-butyllithium

ethyl 7-bromo-2,3-dihydro-1-benzoxepine-4-carboxylate

4-ethylphenyl borate

potassium carbonate

tributyl borate

→

ethyl 7-(4-ethylphenyl)-2,3-dihydro-1-benzoxepine-4-carboxylate

Rendement 85.5%

Solvants

tetrahydrofuran

toluene-ethanol water

tetrahydrofuran

Conditions de réaction

Traitement

1. 1
   workup.STIRRINGstirred at room temperature for 2 hours
2. 2
   workup.STIRRINGthe mixture was stirred for 1 hour
3. 3
   ExtractionThe mixture was extracted with ethyl acetate
4. 4
   LavageThe organic layer was washed with saturated sodium chloride solution
5. 5
   Séchagedried with magnesium sulfate
6. 6
   Concentrationconcentrated under reduced pressure
7. 7
   workup.DISSOLUTIONThe residue was dissolved in acetone (30 ml)
8. 8
   workup.ADDITIONto the mixture was added 10% sulfuric acid (50 ml)
9. 9
   workup.STIRRINGThe mixture was stirred at room temperature for 16 hours
10. 10
    Autreunder reduced pressure acetone was evaporated
11. 11
    ExtractionThe mixture was extracted with ethyl acetate
12. 12
    LavageThe organic layer was washed with saturated sodium chloride solution
13. 13
    Séchagedried with magnesium sulfate
14. 14
    Concentrationconcentrated under reduced pressure
15. 15
    AutreThe residue was separated
16. 16
    Autrepurified with column chromatography (ethyl acetate/hexane=1:2)
17. 17
    Autreto give crude 4-ethylphenyl borate (0.91 g) as colorless solid
18. 18
    Températurethe mixture was refluxed for 18 hours
19. 19
    Températurecooled to room temperature
20. 20
    LavageThe organic layer was washed with saturated sodium chloride solution
21. 21
    Séchagedried with magnesium sulfate
22. 22
    Concentrationconcentrated under reduced pressure
23. 23
    AutreThe residue was separated
24. 24
    Autrepurified with column chromatography (ethyl acetate/hexane=1:15)

Mode opératoire

Under argon atmosphere, to a solution of 4-ethylbromobenzene (10.0 g) in tetrahydrofuran (60 ml) was added n-butyllithium (1.6M hexane solution) (37.2 ml) at −78° C., and the mixture was stirred for 1 hour. To the reaction mixture was dropwise added a solution of tributyl borate (13.68 g) in tetrahydrofuran (30 ml), and the reaction mixture was warmed to room temperature and stirred at room temperature for 2 hours. To the reaction mixture was added 10% sulfuric acid (100 ml), and the mixture was stirred for 1 hour. The mixture was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried with magnesium sulfate and concentrated under reduced pressure. The residue was dissolved in acetone (30 ml), and to the mixture was added 10% sulfuric acid (50 ml). The mixture was stirred at room temperature for 16 hours, and under reduced pressure acetone was evaporated. The mixture was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried with magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified with column chromatography (ethyl acetate/hexane=1:2) to give crude 4-ethylphenyl borate (0.91 g) as colorless solid. Under argon atmosphere, a solution of ethyl 7-bromo-2,3-dihydro-1-benzoxepine-4-carboxylate (500 mg), the above crude 4-ethylphenyl borate (0.32 g) and potassium carbonate (0.49 g) in toluene-ethanol-water (20-2-2 ml) was stirred at room temperature for 1 hour. To the reaction mixture was added tetrakistriphenyl-phosphinepalladium (0.06 g), and the mixture was refluxed for 18 hours and cooled to room temperature. The organic layer was washed with saturated sodium chloride solution, dried with magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified with column chromatography (ethyl acetate/hexane=1:15) to give ethyl 7-(4-ethylphenyl)-2,3-dihydro-1-benzoxepine-4-carboxylate (464 mg) as colorless crystals.

Source